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Vectisol formulation enhances solubility of resveratrol and brings its benefits to kidney transplantation in a preclinical porcine model

David Soussi 1, 2, 3 Jérôme Danion 1, 2, 3 Edouard Baulier 1 Frédéric Favreau 4 Ysé Sauvageon 1, 2, 5 Valentin Bossard 1, 2, 5 Xavier Matillon 1, 6 Frédéric Turpin 7 El Mustapha Belgsir 7 Raphael Thuillier 1, 2, 3, 8 Thierry Hauet 1, 2, 3, 8, 9
8 FHU SUPORT - Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation
CHU Poitiers - Centre hospitalier universitaire de Poitiers , CHRU TOURS - Centre Hospitalier Régional Universitaire de Tours, RESINFIT - Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques, CHU Limoges, IPPRITT - Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation, IRTOMIT - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques, Cellules Dendritiques, Immunomodulation et Greffes
Abstract : Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol ® is a novel antioxidant strategy based on the encapsulation of resveratrol into a cyclodextrin, increasing its bioavailability. We tested this compound as an additive to the most popular static preservation solutions and machine perfusion (LifePort) in a preclinical pig model of kidney autotransplantation. In regard to static preservation, supplementation improved glomerular filtration and proximal tubular function early recovery. Extended follow-up confirmed the higher level of protection, slowing chronic loss of function (creatininemia and proteinuria) and the onset of histological lesions. Regarding machine perfusion, the use of Vectisol ® decreased oxidative stress and apoptosis at the onset of reperfusion (30 min post declamping). Improved quality was confirmed with decreased early levels of circulating SOD (Superoxide Dismutase) and ASAT (asparagine amino transferase). Supplementation slowed the onset of chronic loss of function, as well as interstitial fibrosis and tubular atrophy. The simple addition of Vectisol ® to the preservation solution significantly improved the performance of organ preservation, with long-term effects on the outcome. This strategy is thus a key player for future multi-drug therapy aimed at ischemia reperfusion in transplantation.
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David Soussi, Jérôme Danion, Edouard Baulier, Frédéric Favreau, Ysé Sauvageon, et al.. Vectisol formulation enhances solubility of resveratrol and brings its benefits to kidney transplantation in a preclinical porcine model. International Journal of Molecular Sciences, MDPI, 2019, 20 (9), pp.2268. ⟨10.3390/ijms20092268⟩. ⟨hal-02968028⟩



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